The long-term objective of this project is to understand the anatomical basis for sound localization. Two important cues for the localization of sounds are differences at the two ears in the time of arrival and in the intensity of acoustic stimuli. The goal of this proposal is to study the synaptic connections between the spherical and globular cells of the cochlear nucleus and the neurons in the superior olivary complex that appear to be involved in analyzing these binaural cues. The spherical and globular cells receive monaural inputs, but their axons converge onto single neurons in the lateral and medial superior olivary nuclei, where information from the two sides can be compared. Neurons in the lateral superior olivary nucleus (LSO) respond best to interaural differences in the intensity of a stimulus, whereas neurons in the medial superior olivary nucleus (MSO) respond best to specific interaural differences in the time of arrival of a stimulus. These response properties of the neurons in the LSO and MSO depend on the integration of excitatory and inhibitory synaptic inputs. The thesis of this application is that, although the response properties of the neurons in the LSO and MSO to binaural stimuli are different, both get their excitatory and inhibitory inputs from essentially the same sources in the cochlear nucleus. The differences, then, must depend in large part on differences in the synaptic organization of the inputs. Studies of these differences in the MSO and LSO will contribute to an understanding of the mechanism of integration of excitatory and inhibitory synaptic inputs in the mammalian central nervous system. The specific aims of this application can be summarized as follows: (1) To analyze the synaptic organization of the lateral nucleus of the trapezoid body, a nucleus that may project to the MSO and represent a source of inhibitory input; (2) To characterize the putative inhibitory projections from the lateral nucleus of the trapezoid body into the medial superior olivary nucleus; and 3) To compare the excitatory and inhibitory projections to the MSO and LSO in order to identify differences in the synaptic organization that could lead to the different response properties characteristic of these two nuclei. Methodology used to achieve these aims will include electron microscopy of both normal and experimental material and neuroanatomical tracing techniques based on axonal transport.